Interaction effect of serum serotonin level and age on the 12-week pharmacotherapeutic response in patients with depressive disorders

Despite the recognized antidepressant role of serotonin (5-hydroxytryptamine [5-HT]) signaling pathways in the central nervous system, the association between baseline peripheral 5-HT level and the antidepressant treatment response in clinical studies remains debatable. We investigated the interaction effects of baseline serum 5-HT level and age on the 12-week remission in outpatients with depressive disorders who received stepwise antidepressant treatment. Baseline serum serotonin levels were measured and the age of 1094 patients recorded. The patients received initial antidepressant monotherapy; then, patients with an insufficient response or who experienced uncomfortable side effects received alternative treatments every 3 weeks (3, 6, and 9 weeks). Subsequently, 12-week remission, defined as a Hamilton Depression Rating Scale (HAMD) score of ≤ 7, was evaluated. Individual and interaction effects of serum 5-HT level (as a binary [low vs. high, based on the median value of 72.6 ng/mL] or continuous variable) and age (as a binary [< 60 vs. ≥ 60 years] or continuous variable) on the 12-week remission rate were analyzed using logistic regression models after adjusting for relevant covariates. High 5-HT (≥ 72.6 ng/mL) and age ≥ 60 years were associated with the highest 12-week remission rates and a significant multiplicative interaction effect. The interaction effect of the two variables on the 12-week remission rate was significant even when analyzed as a continuous variable. Our study suggests that the association between baseline serum 5-HT level and 12-week antidepressant treatment outcomes differs according to patient age.

Metabolomic impacts of branched-chain amino acid supplementation during endurance exercise: a crossover study

BackgroundSerotonin syntheses in the brain requires a steady supply of tryptophan. Branched chain amino acids (BCAA) and tryptophan are transported across the blood-brain barrier by the amino acid transporter LAT1. BCAA supplementation is predicted to decrease serotonin biosynthesis through LAT1 competition and reduce central fatigue during exercise. Despite a strong theoretical basis for BCAA to attenuate serotonin production and fatigue during exercise, a number of human clinical trials have failed to demonstrate these benefits. To shed light on this discrepancy, we measured the impact of BCAA supplementation on serotonin and associated metabolites during exercise.MethodsA cohort of endurance runners (n=10) participated in a randomized, placebo-controlled, crossover trial to determine impact of BCAA supplementation during a 60-minute run at 65% of VO2 max. Metabolomic analysis targeted for serotonin and untargeted analysis for biomarkers of BCAA supplementation using LCMS were performed on serum samples collected immediately before and after exercise.ResultsSerum BCAA levels were greater in the supplement group compared to placebo (p<0.05). Serum serotonin was lower immediately after BCAA supplementation and before exercise (p<0.05) but not after exercise. L-ornithine increased during exercise with BCAA treatment compared to placebo. Ratings of perceived exertion were no different in BCAA and placebo groups.ConclusionsBCAA supplementation led to a rapid decrease in serum serotonin concentration relative to placebo, which may be indicative of a central nervous system (CNS) mediated process. After exercise with BCAA supplementation, endurance athletes did not show lower serum serotonin concentration, but did present an almost three-fold increase in L-ornithine which has metabolic connections to cortisol and central fatigue.Trial Registration: ClinicalTrials.gov NCT04969536, retrospectively registered 20 July 2021, https://clinicaltrials.gov/ct2/show/NCT04969536

Role of Serotonin Hormone at Development of Diabetes Mellitus Type 2 disease

Subject :Diabetes Mellitus (DM) type 2 is most common disease characterized by elevation of serum glucose level due to impair insulin production or impair cell response to insulin .Serotonin is hormonal neurotransmitter commonly found in brain cell but it also present in beta cells of pancreas . It is key hormone that stabilizes mood, feelings of well-being, and happiness . Objective of the Study: Role of serotonin in development of DM type 2 disease . Materials and Methods: This study was done on 30 patients with un-control DM type2 patients and 30 control DM type 2 patients , the all subjects age within this study were more than 50 years of both genders .After obtained serum , immediately used quantity method for measured level of serum serotonin concentration . Results: This study shows reduce of serum serotonin concentration level in un-control DM type 2 group compare with control group . Conclusion: This study confirms that decreased serum serotonin concentration level can act as support development of DM type 2 disease .

Effect of Bacillus coagulans Unique IS-2 in Inflammatory Bowel Disease (IBD): A Randomized Controlled Trial

Probiotic intervention is an important approach for the treatment and health restoration in inflammatory bowel disease (IBD). The preventive and therapeutic effects of probiotic Bacillus coagulans Unique IS-2 in different diseases have been well recognized but its efficacy in IBD is unreported. Therefore, a study was conducted to assess the effect of Bacillus coagulans Unique IS-2 in IBD patients. Subjects those satisfying compliance criteria were recruited in the study and given either probiotic B. coagulans Unique IS-2 or placebo for 4 weeks as per randomization. Survival of the given probiotic strain in GI, presence of beneficial gut bacteria, serum cytokines, serum serotonin and serum dopamine, symptoms of disease, physical, behavioral and psychological parameters of the subjects were evaluated before and after intervention. In this study B. coagulans Unique IS-2 was well tolerated with no severe adverse events in IBD patients. B coagulans Unique IS-2 demonstrated good survival in GI tract by significantly high detection in probiotic treated group (p <0.001). Significant enhancement in beneficial Lactobacilli was observed in probiotic treated group (p <0.01). NGS data and metagenomic analysis also showed an increase in the abundance of bacterial genera Bacillus, Lactobacillus, Bifidobacterium, Faecalibacterium, Bacteroides, Megamonas, Lachnospira, Blautia and Alistipes in the post intervention samples in the treatment group. A decrease in in the abundance of bacterial genera Sutterella, Dialister, Roseburia and Megasphaera was observed in post intervention samples in the treatment group. Increased secretion of cytokine IL-10 and variable decrease in the secretion of IL-6, IL-1β, TNF- α, IL -17 and IL -23 was observed in in the probiotic treated group. Post intervention change in serum serotonin and serum dopamine was not significant in both the groups. A reduction in the severity of disease symptoms and improvement in the physical, behavioral and psychological parameter was observed in the probiotic treated group. The observed results demonstrated that B. coagulans Unique IS-2 with SMT was effective in adult IBD patients. Study was registered with Clinical Trials Registry India (CTRI) - (registration reference- REF/2016/09/012181, CTRI registration No.- CTRI/2019/11/022087).

Serotonin Levels in the Serum of Persons with Onchocerciasis-Associated Epilepsy: A Case-Control Study

Onchocerciasis-associated epilepsy (OAE) is a devastating childhood disorder occurring in areas with high Onchocerca volvulus transmission. Despite epidemiological evidence showing the association between O. volvulus and epilepsy, the underlying mechanism remains unknown. Since high levels of serotonin are known to induce seizures, we investigated serotonin levels in persons with OAE and controls selected from the Democratic Republic of Congo. Serum serotonin levels were determined by ELISA in 19 persons with OAE, 32 persons with epilepsy without O. volvulus infection, 18 with O. volvulus infection but without epilepsy, and 35 with neither O. volvulus infection nor epilepsy. O. volvulus infection was diagnosed by skin snip testing and/or OV16 antibody detection. Serum serotonin levels were significantly decreased in persons with OAE compared to persons with O. volvulus infection and no epilepsy. In conclusion, an increased serotonin level is unable to explain the pathogenesis of OAE. Other hypotheses to identify the causal mechanism of OAE will need to be investigated.

Effect of a Cytoprotective Dose of Dehydroleucodine, Xanthatin, and 3-Benzyloxymethyl-5H-furan-2-one on Gastric Mucosal Lesions Induced by Mast Cell Activation

The aim of this study was to determine whether the lactones dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one, would be effective in an animal model of gastric ulcer induced by mast cell activation. Rats were divided into ten groups. Treatments were repeated for four days. The degree of gastric erosion was assessed with a scoring system and histological preparations. Gastric mast cell morphology was analyzed by histological procedures. Serum serotonin levels were determined as markers of mast cell activation. Statistical analyses were done using ANOVA and Tukey–Kramer test. We demonstrated that the repeated administration of compound 48/80 results in extensive mucosal lesions in the gastric mucosa and that such lesions occurred in association with mast cell degranulation and a significant increase of serum serotonin. We showed that these lesions were prevented by dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one and that this effect was similar to that obtained with sodium cromoglycate. In conclusion, the results of the present study indicate that the optimal gastric cytoprotective dose of dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one is efficacious in an animal model of gastric ulcer induced by mast cell activation. Our findings suggest that these lactones could be valuable tools for designing novel therapeutic agents for digestive disorders associated with inappropriate mast cell activation.